Severity of withdrawal symptoms from alcohol was quantified in alcoholics admitted to the Neurology Ward of the Washington, D.C. VA Hospital. Cerebrospinal fluid (CSF) samples were repeatedly obtained early during withdrawal and after all symptoms had subsided. Concentrations of the monoamine neurotransmitter norepinephrine and its major metabolite MHPG were measured at NIH. Significant positive correlations were observed between indices of elevated norepinephrine turnover and several signs of alcohol withdrawal. We are continuing this work trying to identify causes for the noradrenergic dysregulation during alcohol withdrawal. Thus, we are measuring peptides and prostaglandins, known to participate in the regulation of the functioning of noradrenergic synapses simultaneously with norepinephrine. We are correlating the concentrations of these neuromodulators to concentrations of norepinephrine and MHPG in the CSF and to the severity of withdrawal symptoms in our patients. We have completed this phase of the study in six patients and are aiming to increase our sample size to fifteen.